The studies proposed are designed to invesigate the relationship between changes in tumor cell kinetics following cytoreductive tumor surgery and the most efficacious time for initiation of adjuvant chemotherapy. Sequential chemo- and radiotherapy designed on the basis of cell kinetic perturbation in advanced disease will form the basis for adjuvant chemo and radiotherapy schedules. Potentially advantageous times for the initiation of adjuvant treatment will be predicted on the basis of changes in the cell kinetics after cytoreduction. Predictions of efficacious and nonefficacious times will be tested in prospective treatment studies. We will use four animal breast cancer models which will permit comparison of spontaneous and transplantable murine tumors, fast and slowly proliferating murine tumors and respones in mouse and rat models with similar proliferative rates. We will utilize our proven battery of cell kinetic measurements for 3H-TdR LI, DNA synthesis time, PDP index (growth fraction estimate) and mitotic index, all of which can be derived using in vitro methodologies on tumor specimens at the time of surgery. The study has direct significance for the timing of adjuvant chemotherapy and chemotherapy for advanced disease in humans. Since this timing will be within a few days of the surgical procedure, initiation of early adjuvant treatments would be a direct surgical responsibility. This proposal is in reference to RFA NIH-NCI-DCT-7.